Cellular defense against excessive peroxynitrite generation is required to protect against DNA strand-breaks and mutations and against interference with protein tyrosine-based sig naling and other protein functions due to formation of 3-nitrotyrosine. We recently demon strated a role of selenium-containing enzymes catalyzing peroxynitrite reduction. Glutathione peroxidase (GPx) protected against the oxidation of dihydrorhodamine 123 (D H R) by perox ynitrite more effectively than ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a selenoor-ganic compound exhibiting a high second-order rate constant for the reaction with peroxynit rite, 2 × 106 M-1 S-1. The maintenance of protection by GPx against peroxynitrite requires GSH as reductant. Similarly, selenomethionine but not selenomethionine oxide exhibited inhibition of rhodamine 123 formation from DHR caused by peroxynitrite. In steady-state experiments, in which peroxynitrite was infused to maintain a 0.2 μᴍ con centration, GPx in the presence of GSH, but neither GPx nor GSH alone, effectively inhib ited the hydroxylation of benzoate by peroxynitrite. Under these steady-state conditions peroxynitrite did not cause loss of ‘classical’ GPx activity. GPx, like selenomethionine, pro tected against protein 3-nitrotyrosine formation in human fibroblast lysates, shown in Western blots. The formation of nitrite rather than nitrate from peroxynitrite was enhanced by GPx , ebselen or selenomethionine. The selenoxides can be effectively reduced by glutathione, establishing a biological line of defense against peroxynitrite. The novel function of GPx as a peroxynitrite reductase may extend to other selenoproteins containing selenocysteine or selenomethionine. Recent work on organotellurium compounds revealed peroxynitrite reductase activity as well. Inhibition of dihydrorhodamine 123 oxidation correlated well with the GPx-like activity of a variety of diaryl tellurides.
Experimental evidence is provided that selenomethionine oxide (MetSeO) is more readily reducible than its sulfur analogue, methionine sulfoxide (MetSO). Pulse radiolysis experiments reveal an efficient reaction of MetSeO with one-electron reductants, such as e(aq)-, (k = 1.2x10(10) M(-1) s(-1)), CO2*- (k = 5.9x10(8) M(-1) s(-1)) and (CH3)2 C*OH (k = 3.5x10(7) M(-1) s(-1)), forming an intermediate selenium-nitrogen coupled zwitterionic radical with the positive charge at an intramolecularly formed Se(three-electron bond)N 2sigma/1sigma* three-electron bond, which is characterized by an optical absorption with lambda(max) at 375 nm, and a half-life of about 70 micros. The same transient is generated upon HO* radical-induced one-electron oxidation of selenomethionine (MetSe). This radical thus constitutes the redox intermediate between the two oxidation states, MetSeO and MetSe. Time-resolved optical data further indicate sulfur-selenium interactions between the Se(three-electron bond)N transient and GSH. The Se(three-electron bond)N transient appears to play a key role in the reduction of selenomethionine oxide by glutathione.
With the introduction of heart valve prostheses cardiac valvular disease has become much more accessible to therapeutic options. However, currently available prostheses display significant limitations, such as limited long-term durability (biological prostheses) and a long-term necessity for anticoagulation therapy. Hence, alternative prosthesis types have been extensively explored in recent years particularly aiming at the development of vital and regenerative prostheses by means of tissue engineering. In the scientific field, different competing concepts have been introduced, including biological or synthetic scaffolds which can be further enhanced by cellular or extracellular components to promote further in vivo development of the prosthesis after implantation. Nowadays, decellularized donor heart valves are among the most advanced prosthesis types experiencing growing clinical attention and widespread use.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.